Chromatographic alignment of LC-MS and LC-MS/MS datasets by genetic algorithm feature extraction

Liquid chromatography-mass spectrometry (LC-MS) datasets can be compared or combined following chromatographic alignment. Here we describe a simple solution to the specific problem of aligning one LC-MS dataset and one LC-MS/MS dataset, acquired on separate instruments from an enzymatic digest of a protein mixture, using feature extraction and a genetic algorithm. First, the LC-MS dataset is searched within a few ppm of the calculated theoretical masses of peptides confidently identified by LC-MS/MS. A piecewise linear function is then fitted to these matched peptides using a genetic algorithm with a fitness function that is insensitive to incorrect matches but sufficiently flexible to adapt to the discrete shifts common when comparing LC datasets. We demonstrate the utility of this method by aligning ion trap LC-MS/MS data with accurate LC-MS data from an FTICR mass spectrometer and show how hybrid datasets can improve peptide and protein identification by combining the speed of the ion trap with the mass accuracy of the FTICR, similar to using a hybrid ion trap-FTICR instrument. We also show that the high resolving power of FTICR can improve precision and linear dynamic range in quantitative proteomics. The alignment software, msalign, is freely available as open source.

Alignment of a model amyloid peptide fragment in bulk and at a solid surface

The alignment of model amyloid peptide YYKLVFFC is investigated in bulk and at a solid surface using a range of spectroscopic methods employing polarized radiation. The peptide is based on a core sequence of the amyloid beta (A beta) peptide, KLVFF. The attached tyrosine and cysteine units are exploited to yield information on alignment and possible formation of disulfide or dityrosine links. Polarized Raman spectroscopy on aligned stalks provides information on tyrosine orientation, which complements data from linear dichroism (LD) on aqueous solutions subjected to shear in a Couette cell. LD provides a detailed picture of alignment of peptide strands and aromatic residues and was also used to probe the kinetics of self-assembly. This suggests initial association of phenylalanine residues, followed by subsequent registry of strands and orientation of tyrosine residues. X-ray diffraction (XRD) data from aligned stalks is used to extract orientational order parameters from the 0.48 nm reflection in the cross-beta pattern, from which an orientational distribution function is obtained. X-ray diffraction on solutions subject to capillary flow confirmed orientation in situ at the level of the cross-beta pattern. The information on fibril and tyrosine orientation from polarized Raman spectroscopy is compared with results from NEXAFS experiments on samples prepared as films on silicon. This indicates fibrils are aligned parallel to the surface, with phenyl ring normals perpendicular to the surface. Possible disulfide bridging leading to peptide dimer formation was excluded by Raman spectroscopy, whereas dityrosine formation was probed by fluorescence experiments and was found not to occur except under alkaline conditions. Congo red binding was found not to influence the cross-beta XRD pattern.

Steady periodic water waves with constant vorticity: regularity and local bifurcation

This paper studies periodic traveling gravity waves at the free surface of water in a flow of constant vorticity over a flat bed. Using conformal mappings the free-boundary problem is transformed into a quasilinear pseudodifferential equation for a periodic function of one variable. The new formulation leads to a regularity result and, by use of bifurcation theory, to the existence of waves of small amplitude even in the presence of stagnation points in the flow.

De-agrarianization, re-agrarianization and local economic development: re-orientating livelihoods in African artisanal mining communities

This article contributes to the debate on livelihood diversification in rural sub-Saharan Africa, focusing specifically on the growing economic importance of artisanal and small-scale mining (ASM) in the region. The precipitous decline in the value of many export crops and the removal of subsidies on crucial inputs such as fertilizers have made smallholder production unviable, forcing many farmers to ‘branch out’ into non-farm activities to supplement their incomes. One of the more popular destinations for poor farmers is the low-tech ASM sector which, because of its low barriers to entry, has absorbed millions of rural Africans over the past two decades, the majority of whom are engaged in the extraction of near-surface mineral deposits located on concessions that have been demarcated to multinational corporations. The efforts made hitherto to control this illegal mining activity, both through force and regulation, however, have had little effect, forcing many of the region’s governments and private sector partners to ‘re-think’ their approaches. One strategy that has gained considerable attention throughout the region is intensified support for agrarian-orientated activities, many of which, despite the problems plaguing smallholder agricultural sector and challenges with making it more economically sustainable, are being lauded as appropriate ‘alternative’ sources of employment to artisanal mining. After examining where artisanal mining fits into the de-agrarianization ‘puzzle’ in sub-Saharan Africa, the article critiques the efficacy of ‘re-agrarianization’ as a strategy for addressing the region’s illegal mining problem. A case study of Ghana is used to shed further light on these issues.

Optimal control of a class of discrete–continuous non-linear systems — decomposition and hierarchical structure

A technique is derived for solving a non-linear optimal control problem by iterating on a sequence of simplified problems in linear quadratic form. The technique is designed to achieve the correct solution of the original non-linear optimal control problem in spite of these simplifications. A mixed approach with a discrete performance index and continuous state variable system description is used as the basis of the design, and it is shown how the global problem can be decomposed into local sub-system problems and a co-ordinator within a hierarchical framework. An analysis of the optimality and convergence properties of the algorithm is presented and the effectiveness of the technique is demonstrated using a simulation example with a non-separable performance index.

Improvement of 3D protein models using multiple templates guided by single-template model quality assessment

Motivation: Modelling the 3D structures of proteins can often be enhanced if more than one fold template is used during the modelling process. However, in many cases, this may also result in poorer model quality for a given target or alignment method. There is a need for modelling protocols that can both consistently and significantly improve 3D models and provide an indication of when models might not benefit from the use of multiple target-template alignments. Here, we investigate the use of both global and local model quality prediction scores produced by ModFOLDclust2, to improve the selection of target-template alignments for the construction of multiple-template models. Additionally, we evaluate clustering the resulting population of multi- and single-template models for the improvement of our IntFOLD-TS tertiary structure prediction method. Results: We find that using accurate local model quality scores to guide alignment selection is the most consistent way to significantly improve models for each of the sequence to structure alignment methods tested. In addition, using accurate global model quality for re-ranking alignments, prior to selection, further improves the majority of multi-template modelling methods tested. Furthermore, subsequent clustering of the resulting population of multiple-template models significantly improves the quality of selected models compared with the previous version of our tertiary structure prediction method, IntFOLD-TS.

Multi-target out-of-sequence data association: tracking using graphical models

When performing data fusion, one often measures where targets were and then wishes to deduce where targets currently are. There has been recent research on the processing of such out-of-sequence data. This research has culminated in the development of a number of algorithms for solving the associated tracking problem. This paper reviews these different approaches in a common Bayesian framework and proposes an architecture that orthogonalises the data association and out-of-sequence problems such that any combination of solutions to these two problems can be used together. The emphasis is not on advocating one approach over another on the basis of computational expense, but rather on understanding the relationships among the algorithms so that any approximations made are explicit. Results for a multi-sensor scenario involving out-of-sequence data association are used to illustrate the utility of this approach in a specific context.

Multi-target out-of-sequence data association

In data fusion systems, one often encounters measurements of past target locations and then wishes to deduce where the targets are currently located. Recent research on the processing of such out-of-sequence data has culminated in the development of a number of algorithms for solving the associated tracking problem. This paper reviews these different approaches in a common Bayesian framework and proposes an architecture that orthogonalises the data association and out-of-sequence problems such that any combination of solutions to these two problems can be used together. The emphasis is not on advocating one approach over another on the basis of computational expense, but rather on understanding the relationships between the algorithms so that any approximations made are explicit.

Striving for inclusive design in the built environment: learning strategy adopted by policy implementers at local authorities in England

The research will explore views on inclusive design policy implementation and learning strategy used in practice by Local Authorities’ planning, building control and policy departments in England. It reports emerging research findings. The research aim was developed from an extensive literature review, and informed by a pilot study with relevant Local Authority departments. The pilot study highlighted gaps within the process of policy implementation, a lack of awareness of the process and flaws in the design guidance policy. This has helped inform the development of a robust research design using both a survey and semi-structured interviews. The questionnaire targeted key employees within Local Authorities designed to establish how employees learn about inclusive design policy and to determine their views on current approaches of inclusive design policy implementation adopted by their Local Authorities. The questionnaire produces 117 responses. Interestingly approximately 9 out of 129 Local Authorities approached claimed that they were unable to participate either because an inclusive design policy was not adopted or they were faced with a high workload and thus unable to take part. An emerging finding is a lack of understanding of inclusive design problems, which may lead to problem with inclusive design policy implementation, and thus adversely affect how the built environment can be experienced. There is a strong indication from the survey respondents indicating that they are most likely to learn about inclusive design from policy guides produced by their Local Authorities and from their colleagues.

Balanced excitation and inhibition: Model based analysis of local field potentials

We have developed a model of the local field potential (LFP) based on the conservation of charge, the independence principle of ionic flows and the classical Hodgkin–Huxley (HH) type intracellular model of synaptic activity. Insights were gained through the simulation of the HH intracellular model on the nonlinear relationship between the balance of synaptic conductances and that of post-synaptic currents. The latter is dependent not only on the former, but also on the temporal lag between the excitatory and inhibitory conductances, as well as the strength of the afferent signal. The proposed LFP model provides a method for decomposing the LFP recordings near the soma of layer IV pyramidal neurons in the barrel cortex of anaesthetised rats into two highly correlated components with opposite polarity. The temporal dynamics and the proportional balance of the two components are comparable to the excitatory and inhibitory post-synaptic currents computed from the HH model. This suggests that the two components of the LFP reflect the underlying excitatory and inhibitory post-synaptic currents of the local neural population. We further used the model to decompose a sequence of evoked LFP responses under repetitive electrical stimulation (5 Hz) of the whisker pad. We found that as neural responses adapted, the excitatory and inhibitory components also adapted proportionately, while the temporal lag between the onsets of the two components increased during frequency adaptation. Our results demonstrated that the balance between neural excitation and inhibition can be investigated using extracellular recordings. Extension of the model to incorporate multiple compartments should allow more quantitative interpretations of surface Electroencephalography (EEG) recordings into components reflecting the excitatory, inhibitory and passive ionic current flows generated by local neural populations.

The full infinite dimensional moment problem on semi-algebraic sets of generalized functions

We consider a generic basic semi-algebraic subset S of the space of generalized functions, that is a set given by (not necessarily countably many) polynomial constraints. We derive necessary and sufficient conditions for an infinite sequence of generalized functions to be realizable on S, namely to be the moment sequence of a finite measure concentrated on S. Our approach combines the classical results about the moment problem on nuclear spaces with the techniques recently developed to treat the moment problem on basic semi-algebraic sets of Rd. In this way, we determine realizability conditions that can be more easily verified than the well-known Haviland type conditions. Our result completely characterizes the support of the realizing measure in terms of its moments. As concrete examples of semi-algebraic sets of generalized functions, we consider the set of all Radon measures and the set of all the measures having bounded Radon–Nikodym density w.r.t. the Lebesgue measure.

ReadingAct RGB-D action dataset and human action recognition from local features

For general home monitoring, a system should automatically interpret people’s actions. The system should be non-intrusive, and able to deal with a cluttered background, and loose clothes. An approach based on spatio-temporal local features and a Bag-of-Words (BoW) model is proposed for single-person action recognition from combined intensity and depth images. To restore the temporal structure lost in the traditional BoW method, a dynamic time alignment technique with temporal binning is applied in this work, which has not been previously implemented in the literature for human action recognition on depth imagery. A novel human action dataset with depth data has been created using two Microsoft Kinect sensors. The ReadingAct dataset contains 20 subjects and 19 actions for a total of 2340 videos. To investigate the effect of using depth images and the proposed method, testing was conducted on three depth datasets, and the proposed method was compared to traditional Bag-of-Words methods. Results showed that the proposed method improves recognition accuracy when adding depth to the conventional intensity data, and has advantages when dealing with long actions.

Conditioning and preconditioning of the optimal state estimation problem

Optimal state estimation is a method that requires minimising a weighted, nonlinear, least-squares objective function in order to obtain the best estimate of the current state of a dynamical system. Often the minimisation is non-trivial due to the large scale of the problem, the relative sparsity of the observations and the nonlinearity of the objective function. To simplify the problem the solution is often found via a sequence of linearised objective functions. The condition number of the Hessian of the linearised problem is an important indicator of the convergence rate of the minimisation and the expected accuracy of the solution. In the standard formulation the convergence is slow, indicating an ill-conditioned objective function. A transformation to different variables is often used to ameliorate the conditioning of the Hessian by changing, or preconditioning, the Hessian. There is only sparse information in the literature for describing the causes of ill-conditioning of the optimal state estimation problem and explaining the effect of preconditioning on the condition number. This paper derives descriptive theoretical bounds on the condition number of both the unpreconditioned and preconditioned system in order to better understand the conditioning of the problem. We use these bounds to explain why the standard objective function is often ill-conditioned and why a standard preconditioning reduces the condition number. We also use the bounds on the preconditioned Hessian to understand the main factors that affect the conditioning of the system. We illustrate the results with simple numerical experiments.

Closed-loop feedback computation model of dynamical reputation based on the local trust evaluation in business-to-consumer e-commerce

Trust and reputation are important factors that influence the success of both traditional transactions in physical social networks and modern e-commerce in virtual Internet environments. It is difficult to define the concept of trust and quantify it because trust has both subjective and objective characteristics at the same time. A well-reported issue with reputation management system in business-to-consumer (BtoC) e-commerce is the “all good reputation” problem. In order to deal with the confusion, a new computational model of reputation is proposed in this paper. The ratings of each customer are set as basic trust score events. In addition, the time series of massive ratings are aggregated to formulate the sellers’ local temporal trust scores by Beta distribution. A logical model of trust and reputation is established based on the analysis of the dynamical relationship between trust and reputation. As for single goods with repeat transactions, an iterative mathematical model of trust and reputation is established with a closed-loop feedback mechanism. Numerical experiments on repeated transactions recorded over a period of 24 months are performed. The experimental results show that the proposed method plays guiding roles for both theoretical research into trust and reputation and the practical design of reputation systems in BtoC e-commerce.